enalapril and Weight-Loss

Obesity is a significant risk factor for hypertension and the cardiovascular sequelae of hypertension. Weight loss has been shown to be effective in lowering blood pressure in overweight individuals. The purpose of this study was to show the impact of a weight loss intervention on overall medication requirements for obese, hypertensive patients. This was a substudy of the Hypertension Optimal Treatment (HOT) study. HOT study patients who had a body mass index > or =27 kg/m2 were randomized to receive either the weight loss intervention, which included dietary counseling and group support, or to serve as the control group. Patients' weights and number of medication steps (per HOT protocol) required to achieve target diastolic blood pressure were measured at 3, 6, 12, 18, 24, and 30 months. Patients in the weight loss group lost significantly more weight than the control group only at 6 months (-3.2+/-4.3 v. -1.8+/-2.7 kg [mean +/- SD] for weight loss group versus control, respectively, P = .05). The weight loss group tended to regain weight after the first 6 months of the study. However, patients in the weight loss group used a significantly fewer number of medication steps than the control group at all time intervals except 3 months. Weight loss appears to be a useful tool in blood pressure management in patients who require medication to control their blood pressure.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Body Mass Index; Calcium Channel Blockers; Diet; Disease Progression; Drug Therapy, Combination; Enalapril; Felodipine; Female; Humans; Hypertension; Male; Metoprolol; Middle Aged; Obesity; Risk Factors; Treatment Outcome; Weight Loss

We examined whether reversal of high fat diet, stimulating weight loss, compared to two treatments previously shown to have beneficial effects, could improve glucose utilization and peripheral neuropathy in animal models of obesity and type 2 diabetes. Rats were fed a high fat diet and treated with a low dose of streptozotocin to create models of diet induced obesity or type 2 diabetes, respectively. Afterwards, rats were transferred to a normal diet or treated with enalapril or dietary enrichment with menhaden oil for 12 weeks. Obesity and to a greater extent type 2 diabetes were associated with impaired glucose utilization and peripheral neuropathy. Placing obese rats on a normal diet improved glucose utilization. Steatosis but not peripheral neuropathy was improved after placing obese or diabetic rats on a normal diet. Treating obese and diabetic rats with enalapril or a menhaden oil enriched diet generally improved peripheral neuropathy endpoints. In summary, dietary improvement with weight loss in obese or type 2 diabetic rats was not sufficient to correct peripheral neuropathy. These results further stress the need for discovery of a comprehensive treatment for peripheral neuropathy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Obesity Agents; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diet, Fat-Restricted; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Enalapril; Fish Oils; Hypoglycemic Agents; Male; Neuralgia; Non-alcoholic Fatty Liver Disease; Obesity; Rats, Sprague-Dawley; Streptozocin; Weight Loss

Weight loss in chronic heart failure is linked to impaired survival. We aimed to assess the frequency of weight loss in patients with this disease, whether the degree of weight loss predicts mortality, and whether weight loss can be prevented by angiotensin-converting-enzyme (ACE) inhibitors.. We investigated weight changes in 1929 patients from the SOLVD trial who had chronic heart failure, were free of oedema at baseline, and survived for at least 4 months after trial entry. Meanfollow-up was 35 months (SD 13). We analysed the effect of weight loss at cutpoints of 5%, 7.5%, 10%, 15% (a priori), and 6% (post hoc) to identify which one best predicted outcome. To validate results, we analysed data for 619 patients in the V-HeFT II trial.. 817 (42%) patients in the SOLVD trial had weight loss from baseline of 5% or more. At 8 months follow-up, all cutpoints for weight loss were significantly associated with impaired survival after adjustment for age, sex, New York Heart Association class, left ventricular ejection fraction, and treatment allocation. Weight loss of 6% or more at any time during follow-up was the strongest predictor of impaired survival (adjusted hazard ratio 2.10, 95% CI 1.77-2.49; p<0.0001). Patients on the ACE inhibitor enalapril had a lower hazard of 6% or more weight loss than did those not taking the drug (adjusted reduction 19%, p=0.0054). Results from analyses of V-HeFT II data lent support to our findings.. Weight loss occurs frequently in patients with chronic heart disease, its reversal is rare, and when present, it is independently linked to impaired survival. Weight loss of more than 6% should be used to define the presence of cachexia in patients with chronic heart failure. In chronic heart failure, treatment with an ACE inhibitor reduces the risk of weight loss.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Data Interpretation, Statistical; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Hydralazine; Isosorbide Dinitrate; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Survival Analysis; Weight Loss

This study was conducted to evaluate the mechanisms of weight loss-induced blood pressure (BP) reduction focusing, in particular, on the contributions of sympathetic nervous system activity, fasting plasma insulin, and leptin to BP levels, and to delineate the additional influence of antihypertensive drug therapy. Each of five groups of obese hypertensives were treated with the long-acting calcium channel blocker (CCB) amlodipine, the angiotensin converting enzyme (ACE) inhibitor enalapril with or without a weight reduction program, or a weight reduction program alone. The goal BP was less than 140/90 mm Hg for the pharmacologic treatment groups. The weight reduction program groups with or without pharmacologic treatment were divided into two groups; weight loss groups who succeeded in weight reduction (> or = 10%) and nonweight loss groups who failed in weight reduction (<10%) in the first 6 months. The final dose of CCB and ACE inhibitor were less in the combined pharmacologic and weight loss groups than in the pharmacologic treatment alone groups or in the pharmacologic and nonweight loss groups. In the weight reduction groups regardless of pharmacologic treatment, the percent reductions from baseline in plasma insulin, leptin, and norepinephrine (NE) were greater in the weight loss groups (> or = 10%) than in the nonweight loss groups (<10%). The reductions in plasma NE, insulin, and leptin were significantly greater and earlier in combined pharmacologic and weight loss groups than in the pharmacologic treatment alone groups. In ACE inhibitor groups, the reductions in plasma NE, in insulin, and especially in leptin were greater than the other groups. In the CCB alone group, reductions in insulin and leptin occurred, but there was no change in plasma NE. Reductions in insulin and leptin in CCB groups were less and occurred later than in the ACE inhibitor groups or the weight reduction alone group. These results show that weight loss associated with favorable metabolic improvements and these improvements are amplified when combined with pharmacologic treatment. Therefore, weight loss should be regarded as an essential component of any treatment program for obesity-related hypertension. A novel finding from this study is that ACE inhibition had a striking effect to lower plasma leptin. Suppression of sympathetic activity, insulinemia, and leptinemia appeared to play a role in the BP reduction accompanying weight loss.

Topics: Adult; Amlodipine; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Combined Modality Therapy; Enalapril; Humans; Hypertension; Male; Middle Aged; Obesity; Sympathetic Nervous System; Weight Loss